Ver­sant care­ful­ly sets the stage for a $68M de­but of a biotech play­er fo­cused on syn­thet­ic lethal­i­ty

Over the past 18 months, the grow­ing team at Re­pare Ther­a­peu­tics has been qui­et­ly set­ting up shop in Ver­sant Ven­tures’ dis­cov­ery ops and fo­cus­ing on syn­thet­ic lethal­i­ty — the ther­a­peu­tic in­ter­play be­tween ge­net­ic mu­ta­tions and can­cer. Us­ing CRISPR gene edit­ing tech as an in­ter­ro­ga­tion tool, they’ve been play­ing with well known tar­gets like p53 and BR­CA1 to find out how they con­spire with oth­er mu­ta­tions in the de­struc­tion of a ma­lig­nan­cy, fol­low­ing the trail of le­sions in the pur­suit of new ther­a­pies that can work in the same fun­da­men­tal way those PARP in­hibitors you’ve been hear­ing so much about can fight can­cer.

The goal was to mas­ter syn­thet­ic lethal­i­ty and iden­ti­fy the first cou­ple of tar­gets to go af­ter in the clin­ic. They lined up their team, now at 20, li­censed in dis­cov­ery work from NYU on a poly­merase im­pli­cat­ed in nu­mer­ous can­cers, and to­day will come out of stealth mode with a $68 mil­lion round and at least a four-year run­way with plans to start tack­ling clin­i­cal work in late 2019.

Their first pro­gram in­volves DNA-di­rect­ed DNA poly­merase theta — PolQ — in­clud­ed in a path­way that re­pairs dou­ble-strand breaks in can­cer cells. And while they have a ways to go be­fore they be­gin hu­man stud­ies, the in­vestors are send­ing a mes­sage that the amount of cash they’re bet­ting on Re­pare in­di­cates a high lev­el of con­fi­dence for their longterm suc­cess.

Jer­el Davis

“In terms of the in­cu­ba­tion pe­ri­od,” says Jer­el Davis, man­ag­ing di­rec­tor at Ver­sant, “this com­pa­ny is de­cep­tive­ly ma­ture.”

“The time we’ve been able to spend in stealth al­lowed us to build the com­pa­ny out of the spot­light,” says CEO Lloyd Se­gal. In Mon­tre­al they have de­vel­oped their med­i­c­i­nal chem­istry team un­der Cameron Black, the for­mer head of chem­istry at Mer­ck Frosst who joined a lit­tle more than a year ago. And when Ver­tex re­cent­ly shut down in Mon­tre­al, they swooped in, grab­bing an ex­pe­ri­enced team with a long track record of work­ing to­geth­er.

Lloyd Se­gal

With­in hours of the shut­down, they had 13 new re­cruits out of 14 of­fers.

R&D head Michael Zin­da, who led As­traZeneca On­col­o­gy iMed Bio­science group in Boston, is head­ing up the oth­er group in Cam­bridge, MA.

Ver­sant has gath­ered an im­pres­sive group of mar­quee in­vestors to back their up­start. MPM Cap­i­tal came in along­side as the lead in­vestor on the Se­ries A, with Cel­gene’s Swiss of­fice tak­ing part along with FTQ and BDC Ven­tures.

“We could have tak­en more mon­ey,” Se­gal tells me. “We had more than that on the ta­ble. But we be­lieved that was the kind of mon­ey that we hope will take two com­pounds in­to the clin­ic in late ’19 or ear­ly 2020.”

Ver­sant had a front row seat on some of the ear­ly work on syn­thet­ic lethal­i­ty at Clo­vis while it was work­ing on PARP, says Davis. “This is a field we know and our con­vic­tion is that PARP is the tip off the ice­berg.”

Re­pare has the plat­form that they plan to use to map out some of the rest of the un­ex­plored ter­ri­to­ry.

Even with­out R&D part­ners Se­gal feels that he has enough cash to make their way through at least the first 4 years. Add in the prospect of some ma­jor league play­ers com­ing in to part­ner on key prospects, and that run­way will stretch fur­ther. If it all plays out ac­cord­ing to plan, Se­gal adds, this will be their last ven­ture raise.

It’s an am­bi­tious plan, with some stel­lar sci­en­tif­ic ad­vis­ers ready to leaned guid­ance. The full sci­en­tif­ic ad­vi­so­ry board in­cludes:

– Samuel Apari­cio, pro­fes­sor in the de­part­ment of pathol­o­gy and lab­o­ra­to­ry med­i­cine at the Uni­ver­si­ty of British Co­lum­bia.

– Jim Carmichael, head of the pro­tein home­osta­sis the­mat­ic cen­ter of ex­cel­lence at Cel­gene. He pre­vi­ous­ly was UK re­gion­al di­rec­tor of med­ical sci­ence at As­traZeneca fol­low­ing its ac­qui­si­tion of Ku­DOS, where he was CMO and re­spon­si­ble for clin­i­cal de­vel­op­ment of ola­parib.

– Ron­ny Drap­kin, di­rec­tor of the Penn Ovar­i­an Can­cer Re­search Cen­ter and di­rec­tor of gy­ne­co­log­ic can­cer re­search at the Uni­ver­si­ty of Penn­syl­va­nia.

– Lau­rie Glim­ch­er, pres­i­dent and CEO of the Dana-Far­ber Can­cer In­sti­tute.

– Mark Pe­gram, di­rec­tor of the breast can­cer on­col­o­gy pro­gram at Stan­ford Women’s Can­cer Cen­ter and co-di­rec­tor of Stan­ford’s mol­e­c­u­lar ther­a­peu­tics pro­gram.

– Richard Wood, pro­fes­sor of mol­e­c­u­lar bi­ol­o­gy at the Uni­ver­si­ty of Texas MD An­der­son Can­cer Cen­ter.

Martin Shkreli [via Getty]

Pris­on­er #87850-053 does not get to add drug de­vel­op­er to his list of cred­its

Just days after Retrophin shed its last ties to founder Martin Shkreli, the biotech is reporting that the lead drug he co-invented flopped in a pivotal trial. Fosmetpantotenate flunked both the primary and key secondary endpoints in a placebo-controlled trial for a rare disease called pantothenate kinase-associated neurodegeneration, or PKAN.

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We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology
ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development
CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at with any issues.

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Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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Hal Barron. GSK

GSK's Hal Bar­ron her­alds their sec­ond pos­i­tive piv­otal for cru­cial an­ti-BC­MA ther­a­py, point­ing to a push for quick OKs in a crowd­ed field

Hal Barron has his second positive round of Phase III data in hand for his anti-BCMA antibody drug conjugate belantamab mafodotin (GSK2857916). And GSK’s research chief says the data paves the way for their drive in search of an FDA approval for treating multiple myeloma.

It’s hard to overestimate the importance of this drug for GSK, a cornerstone of Barron’s campaign to make a dramatic impact on the oncology market and provide some long-lost excitement for the pharma giant’s pipeline. They’re putting this BCMA program at the front of that charge — looking to lead a host of rivals all aimed at the same target.

We don’t know what the data are yet, but DREAMM-2 falls on the heels of a promising set of data delivered 5 months ago for DREAMM-1. There investigators noted that complete responses among treatment-resistant patients rose to 15% in the extra year’s worth of data to look over, with a median progression-free survival rate of 12 months, up from 7.9 months reported earlier. The median duration of response was 14.3 months.

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UP­DAT­ED: An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Where do they need the FDA to hus­tle up?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

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Bob Smith, Pfizer

Pfiz­er is mak­ing a $500M state­ment to­day: Here’s how you be­come a lead play­er in the boom­ing gene ther­a­py sec­tor

Three years ago, Pfizer anted up $150 million in cash to buy Bamboo Therapeutics in Chapel Hill, NC as it cautiously stuck a toe in the small gene therapy pool of research and development.

Company execs followed up a year later with a $100 million expansion of the manufacturing operations they picked up in that deal for the UNC spinout, which came with $495 million in milestones.

And now they’re really going for it.

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Video: Putting the AI in R&D — with Badhri Srini­vasan, Tony Wood, Rosana Kapeller, Hugo Ceule­mans, Saurabh Sa­ha and Shoibal Dat­ta

During BIO this year, I had a chance to moderate a panel among some of the top tech experts in biopharma on their real-world use of artificial intelligence in R&D. There’s been a lot said about the potential of AI, but I wanted to explore more about what some of the larger players are actually doing with this technology today, and how they see it advancing in the future. It was a fascinating exchange, which you can see here. The transcript has been edited for brevity and clarity. — John Carroll

As­traZeneca’s Imfinzi/treme com­bo strikes out — again — in lung can­cer. Is it time for last rites?

AstraZeneca bet big on the future of their PD-L1 Imfinzi combined with the experimental CTLA-4 drug tremelimumab. But once again it’s gone down to defeat in a major Phase III study — while adding damage to the theory involving targeting cancer with a high tumor mutational burden.

Early Wednesday the pharma giant announced that their NEPTUNE study had failed, with the combination unable to beat standard chemo at overall survival in high TMB cases of advanced non-small cell lung cancer. We won’t get hard data until later in the year, but the drumbeat of failures will call into question what — if any — future this combination can have left.

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Why would Am­gen want to buy Alex­ion? An­a­lysts call hot­ly ru­mored takeover un­like­ly, but seize the mo­ment

A rumor that Amgen is closing in on buyout deal for Alexion has sparked a guessing game on just what kind of M&A strategy Amgen is pursuing and how much Alexion is worth.

Mizuho analyst Salim Syed first lent credence to the report out of the Spanish news outlet Intereconomía, which said Amgen is bidding as much as $200 per share. While the source may be questionable, “the concept of this happening doesn’t sound too crazy to me,” he wrote.